Abstract

The good coverage and high resolution afforded by functional magnetic resonance imaging (fMRI) make it an excellent tool for the noninvasive imaging of the human brain. Equally interesting, however, is the use of this technique in animal studies using high magnetic fields. In the latter case, highly spatiotemporally resolved fMRI can reveal how widespread neural networks are organized, and accompanying electrophysiological recordings can show how small neural assemblies contribute to this organization.
By applying fMRI and magnetic resonance spectroscopic imaging (MRS) to the nonhuman primate, the most frequently used laboratory animal for the study of the neural basis of cognition, scientists may be able to investigate levels of neural organization that cannot be studied by electrodes alone. These include (1) long-range interactions between different brain structures, (2) task- and learning-related neurochemical changes by means of localized in vivo spectroscopy or MRS, (3) dynamic connectivity patterns by means of labeling techniques involving MR contrast agents, and (4) plasticity and reorganization after experimentally placed focal lesions. Such applications promise to bridge the gap between human neuroimaging studies and the large body of animal research performed over the last half a century. Ultimately, however, the success of fMRI as a tool for visualizing brain function in humans or animals is crucially dependent on a deeper understanding of the relationship between the observed signal and the underlying neuronal activity that we think it represents.
The fMRI technique, like most current brain imaging techniques, capitalizes on the coupling of cerebral blood flow (CBF), energy demand, and neural activity. The interactions between these variables are overwhelmingly complex and involve interrelated factors such as the type of neural activity involved, the cell groups generating this activity, the link between this activity and energy demands, and the processes ultimately coupling the energy demand to the supply of energy to the brain. In this review I will concentrate on only one aspect of this complex issue, namely the type of neural activity that could play a dominant role in the generation of one sort of fMRI signal: the imaging signal capitalizing on the blood oxygen level-dependent (BOLD) contrast mechanism.